Millions of people have taken a direct-to-consumer (DTC) genetic health test to identify their risk of developing cancer or other diseases.
These at-home DNA testing kits are a booming healthcare business with companies like 23andMe, MyHeritage and now Ancestry offering genetic health testing. The global DTC genetic testing market is projected to reach $6.36 billion by 2028, according to BIS Research.
But researchers at medical genetics company Invitae say health reports from limited DTC genetic tests can provide consumers with a false sense of security. These tests often miss disease-causing DNA variants, which poses the risk of healthcare decisions based on incomplete information, according to Edward Esplin, M.D., a clinical geneticist at Invitae and lead researcher on the study.
Esplin presented these findings at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston Oct. 17.
Invitae, the company that conducted the study, is a competitor to 23andMe, one of the largest DTC genetic testing companies. The study was not published and has not been peer reviewed.
"These health reports may provide a false sense of reassurance and should not be used for making any health decisions without confirmation testing,” Esplin said.
23andMe refuted the study’s claims, saying its testing is extremely accurate.
"Our testing process has proven to be over 99% accurate compared to Sanger sequencing, the industry gold standard, and over 99% repeatable and reproducible, per the FDA review process,” Andy Kill, 23andMe spokesman, said in an emailed statement.
Ancestry did not respond to a request for comment.
Many DTC genetic testing companies, including 23andMe, use genotyping, and the limitations of genotyping are well known, Erica Ramos, a personalized medicine expert at the National Society of Genetic Counselors, told FierceHealthcare. There are around 6 billion letters in the whole human genome, and genotyping tests only a subset of that.
The research from Invitae highlights that DTC tests are limited, but that was already known, Ramos said. The study uses the words "false negatives" to describe the DTC genetic testing results—a pretty bold claim, Ramos said. "That implies the test was meant to find something and it doesn’t find what it was meant to find," Ramos said.
23andMe categorically disputes the findings.
"Any claim that 23andMe delivers 'false negatives' for variants that it does not test nor claim to test for is false and misleading," Kill said.
Other companies have jumped into the cancer testing space using whole-genome sequencing. These companies include Invitae, Veritas Genetics and Color, which offers physician-ordered, clinical-grade hereditary cancer tests.
But 23andMe is the only DTC genetic testing service approved by the FDA to provide health reports directly to consumers without a medical professional being involved. It offers 130 total reports based on specific genetic variants and has sold 10 million kits.
On its website, 23andMe said sequencing technology has not yet progressed to the point at which it is feasible to sequence an entire person’s genome "quickly and cheaply enough to keep costs down for consumers."
23andMe is clear with customers that it tests only for certain genetic variants, the company said, and the variants tested in its BRCA1 and BRCA2 report are some of the most well-studied variants, associated with extremely high risk.
A screening tool like 23andMe can be beneficial by identifying risks for people who may not qualify for clinical testing, the company said.
The bigger issue with DTC genetic testing is whether consumers understand what the tests do and do not look for, Ramos said. "Especially as more and more of these tests become available and in the absence of a healthcare provider, that's opening up more doors for confusion as people look at multiple different types of tests," she said.
What the research found
The Invitae study focused on two DTC screening tests authorized by the U.S. Food and Drug Administration. The researchers studied 270,000 patients who, because of a family history of cancer, had been referred to Invitae by physicians for testing of the MUTYH gene that has variants linked to colorectal cancer. They also studied 119,000 patients who had been referred for testing of BRCA1/2.
23andMe tests for two MUTYH variants that are common in people with northern European ancestry and for three BRCA1/2 variants that are common among individuals of Ashkenazi-Jewish descent.
For the research, Invitae performed limited variant DTC screenings and found that most patients would have received clinical "false-negative" results, the researchers claim.
The study found that for MUYTH screening, 40% of individuals with mutations in both of their MUTYH genes, consistent with almost 100% lifetime risk of colorectal cancer, would have been missed. An additional 22% of carriers of one MUTYH mutation, consistent with a twofold increased risk of colorectal cancer, would also have been missed.
For BRCA1/2 testing, nearly 1 in 5 individuals of Ashkenazi-Jewish descent (19%) with a disease-causing variant would have been told none was found, according to researchers. And 94% of non-Ashkenazi Jewish individuals had a BRCA1/2 mutation that would be missed, according to the research.
“A clinical false-negative result can be incorrectly reassuring, excluding a patient from receiving the preventive care they need based on their risk. It could be the difference between preventing cancer and developing cancer,” Esplin said.
Ramos points out that the study looked at data from people who had been referred to genetic testing by a healthcare provider due to personal history or family history of cancer and questioned whether that's applicable to the general population.
"No genetic counselor or other genetics experts would recommend a microarray test [under those circumstances]. It would absolutely not be on the table," she said.
Researchers also analyzed the likelihood that DTC genetic testing could miss a cancer-causing DNA variant among people with different ethnic backgrounds. Researchers concluded that for some ethnic groups, the chance that the testing would not pick up the pathogenic variant was as high as 100%.
For BRCA1/2, a disease-causing variant would have been missed with most ethnic groups, the researchers claim.
Ramos said physicians need to be more involved in conversations around genetic testing and more collaboration is needed between physicians and genetic counselors.
"If a patient's results are negative and they ask their physician, 'did this rule out something in important?', It's important for clinicians to know that the answer, often, is no. If they still have concerns about their health, especially related to family history, they should be referred to a genetic counselor."